Virology Department, Animal and Plant Health Agency, Addlestone, KT15 3NB, UK.
Nuffield Department of Medicine, University of Oxford, Oxford, OX1 3SY, UK.
Sci Rep. 2017 Jan 20;7:40942. doi: 10.1038/srep40942.
Conventional dendritic cells (cDC) are professional antigen-presenting cells that induce immune activation or tolerance. Two functionally specialised populations, termed cDC1 and cDC2, have been described in humans, mice, ruminants and recently in pigs. Pigs are an important biomedical model species and a key source of animal protein; therefore further understanding of their immune system will help underpin the development of disease prevention strategies. To characterise cDC populations in porcine blood, DC were enriched from PBMC by CD14 depletion and CD172a enrichment then stained with lineage mAbs (Lin; CD3, CD8α, CD14 and CD21) and mAbs specific for CD172a, CD1 and CD4. Two distinct porcine cDC subpopulations were FACSorted CD1 cDC (LinCD172 CD1CD4) and CD1 cDC (LinCD172a CD1 CD4), and characterised by phenotypic and functional analyses. CD1 cDC were distinct from CD1 cDC, expressing higher levels of CD172a, MHC class II and CD11b. Following TLR stimulation, CD1 cDC produced IL-8 and IL-10 while CD1 cDC secreted IFN-α, IL-12 and TNF-α. CD1 cDC were superior in stimulating allogeneic T cell responses and in cross-presenting viral antigens to CD8 T cells. Comparison of transcriptional profiles further suggested that the CD1 and CD1 populations were enriched for the orthologues of cDC1 and cDC2 subsets respectively.
传统树突状细胞(cDC)是专业的抗原呈递细胞,可诱导免疫激活或耐受。在人类、小鼠、反刍动物以及最近在猪中,已经描述了两种功能上专门化的群体,称为 cDC1 和 cDC2。猪是一种重要的生物医学模型物种,也是动物蛋白的重要来源;因此,进一步了解其免疫系统将有助于支持疾病预防策略的发展。为了表征猪血液中的 cDC 群体,通过 CD14 耗竭和 CD172a 富集从 PBMC 中富集 DC,然后用谱系 mAb(Lin;CD3、CD8α、CD14 和 CD21)和针对 CD172a、CD1 和 CD4 的 mAb 进行染色。通过流式细胞分选分离出两种不同的猪 cDC 亚群 CD1 cDC(LinCD172 CD1 CD4)和 CD1 cDC(LinCD172a CD1 CD4),并通过表型和功能分析进行表征。CD1 cDC 与 CD1 cDC 不同,表达更高水平的 CD172a、MHC Ⅱ类和 CD11b。在 TLR 刺激后,CD1 cDC 产生 IL-8 和 IL-10,而 CD1 cDC 分泌 IFN-α、IL-12 和 TNF-α。CD1 cDC 更擅长刺激同种异体 T 细胞反应,并将病毒抗原交叉呈递给 CD8 T 细胞。转录谱的比较进一步表明,CD1 和 CD1 群体分别富集了 cDC1 和 cDC2 亚群的同源物。